Seth Darst - September 23, 2020

Seth Darst, PhD, Jack Fishman Professor, The Rockefeller University, "Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex-part II"

The research study discussed the structural basis for helicase-polymerase. Dr. Darst discussed the underlying hypothesis of the structure that multi-subunit cellular (grown-up) DNA-dependent RNA polymerases (DdRps) and backtracking. He first reviewed the literature suggesting that the RNA-DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase (Nudler et al., 1991). Then, Dr. Seth explained the E.Coli RNA polymerase transcription elongation complex, which included the template-strand DNA, RNA transcript, nontemplate-strand DNA, Mg2+, and Bridge helix. Then, he introduced the complex structure by Cheung and Cramer (2012) as the DNA moved backward to show the arrest complex. By explaining the rationale, Dr. Darst explained the backtracking as a proofreading mechanism. The researcher showed that the structure of the SARS-CoV-2 RdRp-RNA was complex. In addition, DdRp backtracking was easy (energetically neutral) and RdRp backtracking was unfavorable. The backtracking was important to support proofreading and facilitate template switching during sub-genomic transcription.